Hydrochloric Acid → [4-Chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester

HRID 23408ノート

反応式

HRID 23408 の反応式
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2].[Li]C(CC)C.CON(C)[C:25](=[O:29])[CH:26]([CH3:28])[CH3:27].Cl>C1COCC1.CCOCC>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH2:15][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 10866371N-Methoxy-N,2-dimethylpropanamideHCID 14710386tert-Butyl (4-chloro-2-methylphenyl)carbamateHCID 178418400CID 53628100

生成物 1

HCID 20756847[4-Chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

Following the procedure described by R. D. Clark et al. in Synthesis, 871 (1991), (4-chloro-2-methyl-phenyl)-carbamic acid tert-butyl ester (2.18 g, 9 mmole) was dissolved in anhydrous THF (30 ml) and cooled to −40° C. and s-BuLi (14.56 ml 1.3N in cyclohexane) was added slowly at such a rate to maintain the temperature below −25° C. The bright yellow solution was cooled to −50° C. and a solution of N-methoxy-N-methyl-isobutyramide (1.24 g, 9.5 mmole) in THF (5 ml) was added. The mixture was allowed to warm up to −10° C. over a 20 m period during which time the solution turned nearly colorless. Ether (50 ml) was added and the solution was poured into 1% aqueous HCl (50 ml). The aqueous layer was extracted a second time with ether (30 ml) and the combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and evaporated to dryness to afford the crude product which was purified by column chromatography (silica gel) eluting with ethyl acetate:hexane (4:1) to afford pure [4-chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester.

後処理

  1. temperatureto maintain the temperature below −25° C
  2. temperatureThe bright yellow solution was cooled to −50° C.
  3. temperatureto warm up to −10° C. over a 20 m period during which time the solution
  4. extractionThe aqueous layer was extracted a second time with ether (30 ml)
  5. washthe combined organic extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto afford the crude product which
  10. customwas purified by column chromatography (silica gel)
  11. washeluting with ethyl acetate:hexane (4:1)

出典と根拠

ORDレコード
ord-5c5dc5b4dfd2421caebb5fb237b64db2
出典データセット
uspto-grants-2005_02
特許番号
US06852726B2

反応ノート

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